αandβSubunits of the Gastric H/K -ATPase Are Concordantly Targeted by Parietal Cell Autoantibodies Associated with Autoimmune Gastritis
作者:
CallaghanJudy M.,
KhanMuhammad A.,
AlderuccioFrank,
Van DrielIan R.,
GleesonPaul A.,
HockBan,
期刊:
Autoimmunity
(Taylor Available online 1993)
卷期:
Volume 16,
issue 4
页码: 289-295
ISSN:0891-6934
年代: 1993
DOI:10.3109/08916939309014648
出版商: Taylor&Francis
关键词: Autoimmunity;H+/K+-ATPase;Autoimmune Gastritis
数据来源: Taylor
摘要:
We have previously shown that parietal cell autoantibodies predominantly react with a 60-90 kDa gastric autoantigen1,2, subsequently identified as the (3 subunit of the gastric H+/K+-ATPase (EC 3.6.1.3) (proton pump)3-5whereas Karlsson et al6showed that these autoantibodies primarily target the 95 kDaαsubunit of the pump. In view of these discordant results, we have reassessed the reactivity of parietal cell autoantibodies with the two subunits of the gastric H+/K+-ATPase. We show here that all 26 parietal cell autoantibody-positive sera immunoblot both subunits under appropriate, but mutually exclusive, conditions. Thus, reactivity of anti- parietal cell autoantibodies with the 95 kDaαsubunit is optimal when the SDS-PAGE is carried out with samples which are reduced but not boiled. Whereas reactivity with the 60-90 kDaβsubunit is optimal with samples which are boiled but not reduced. Autoantibody reactivity with theβsubunit is critically dependent on the presence of a full complement of N-linked glycans since partially deglycosylated protein, and recombinantβsubunit expressed in COS cells, bearing high mannose N-glycans, failed to bind to the autoantibody. These studies also suggest that B cell auto-epitopes are located on the lumenal domain of theβsubunit. Reactivity of parietal cell autoantibodies with a bacterial fusion protein incorporating the catalytic cytoplasmic domain of theαsubunit suggests the presence of auto-epitopes in this region of the molecule.
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